Cellular and Genetic Analysis of Lysosome and Lysosome-Related Organelle Biogenesis in C. Elegans

溶酶体是在几乎所有动物细胞中发现的膜结合区室，其在细胞内和细胞外衍生物质的降解中具有充分表征的作用。 虽然已经了解了很多关于溶酶体在细胞中进行的各种重要过程，但在复杂的多细胞动物中，特别是当它们在胚胎发育期间发育时，溶酶体组装的潜在机制相对未被研究。 为了帮助理解这些过程，Hermann博士正在鉴定和表征模型多细胞生物C的胚胎肠中溶酶体组装所必需的基因。优雅 Hermann实验室已经确定肠道颗粒是一种细胞类型特异性的，与溶酶体相关的细胞器，在脂肪储存中发挥作用。 为了详细了解控制肠道颗粒形成的机制，Hermann实验室分离并表征了一系列在肠道颗粒生物发生中有缺陷的glo突变体。迄今为止，大多数在溶酶体相关细胞器的生物发生中起作用的基因并不是胚胎存活所必需的。赫尔曼实验室已经确定了22个胚胎致死的glo突变体，这些突变体在细胞外错误定位肠道颗粒内容物。 将从分子水平鉴定这些菌株中活性被破坏的肠颗粒形成所需的基因。 对这些基因的研究可能为多细胞生物体中溶酶体生物合成所必需的途径提供新的见解。 近年来对C. elegans提出，卵黄血小板和肠原基中含有LMP-1：：GFP的区室也代表溶酶体相关的细胞器。 将使用显微镜和遗传方法研究含有LMP-1：：GFP的细胞器、卵黄血小板和肠颗粒是否具有常规溶酶体、其他内体隔室或彼此的特征。 如果这三个区室代表不同的溶酶体相关细胞器，胚胎肠将提供一个强大的遗传系统，以研究结构和功能不同的溶酶体区室是如何在同一个细胞中形成的。该项目将涉及25至30名本科生每年独立，动手，原创性研究。 在PI实验室和上师细胞生物学课程（招生24）工作的本科生将进行研究。 这项工作将为所有多细胞动物中可能在溶酶体组装/维持中保留的溶酶体组装提供分子见解。

Lysosomes are membrane bound compartments found in nearly all animal cells that have well characterized roles in the degradation of intra and extra-cellular derived material. While much has been learned regarding the diverse and important processes that lysosomes carry out in cells, the mechanisms underlying the assembly of lysosomes in complex multicellular animals, especially as they develop during embryogenesis, are relatively unstudied. To aid in understanding of these processes, Dr. Hermann is identifying and characterizing genes necessary for the assembly of lysosomes in the embryonic intestine of the model multicellular organism C. elegans. The Hermann lab has identified gut granules as a cell type specific, lysosome-related organelle that functions in the storage of fat. To gain detailed insight into the mechanisms controlling the formation of gut granules the Hermann lab has isolated and is characterizing a collection of glo mutants that are defective in gut granule biogenesis. Most genes identified to date that function in the biogenesis of lysosome-related organelles are not required for embryonic viability. The Hermann lab has identified 22 embryonic lethal glo mutants that extracellularly mislocalize gut granule contents. The genes necessary for the formation of gut granules whose activity is disrupted in these strains will be molecularly identified. Studies of these genes are likely to provide novel insights into the pathways necessary for lysosome biogenesis in multicellular organisms. Recent studies in C. elegans suggest that yolk platelets and LMP-1::GFP containing compartments in the intestinal primordium also represent lysosome-related organelles. Whether LMP-1::GFP containing organelles, yolk platelets, and gut granules have characteristics of conventional lysosomes, other endosomal compartments, or each other will be investigated using microscopic and genetic approaches. If these three compartments represent distinct lysosome-related organelles, the embryonic intestine would provide a powerful genetic system to investigate how structurally and functionally distinct lysosomal compartments are formed in the same cell.The project will involve 25 to 30 undergraduates a year in independent, hands-on, original research. Undergraduate students working in the PI's lab and upper division Cell Biology course (enrollment 24) will carry out the studies. The work will provide molecular insights into the assembly of lysosomes likely to be conserved in the assembly/maintenance of lysosomes in all multicellular animals.